OBJECTIVES/GOALS: Our objective is to explore the evolving role of evaluators within Learning Health Systems (LHSs) and the implications for evaluation approaches in these dynamic healthcare environments. We aim to disseminate lessons learned to help inform best practices for other CTSA hubs operating under a LHS model. METHODS/STUDY POPULATION: Our investigation builds upon our prior qualitative analysis of the LHS literature and contextualization of unique challenges, and potential remedies, of a LHS in Academic Health Centers. As evaluators, we are particularly interested in understanding how evaluation work is conducted in LHSs and exploring ways to optimize the role of evaluators and their skillset in this context. For this investigation, we examined the competencies necessary for evaluators working in LHS and the specialized evaluation approaches needed to fulfill these requirements. Our approach drew from multi-faceted data and experience. We leveraged insights from our literature review, direct experience within WFUSOM CTSI, and discussions with other evaluators. This combination of data sources provided the foundation for our analysis. RESULTS/ANTICIPATED RESULTS: We expect that as more health systems move toward the LHS model, they will have an increased need for various forms of evaluation, requiring resources well beyond what they are currently dedicating to evaluation. Expectations for evaluators will be enhanced in the following distinct, yet complementary, categories: generating new knowledge and translating research knowledge into practice. Anticipated results include identifying essential competencies for evaluators in LHS, such as data proficiency, clinical understanding, and adaptive skills. We also expect to uncover various evaluation approaches specific to LHS, including quality improvement studies, pragmatic trials, and stakeholder-engaged research. DISCUSSION/SIGNIFICANCE: Understanding the evolving role of evaluators and specialized evaluation approaches in LHS is crucial. It enhances the ability to generate localized evidence, customize interventions, and improve patient care. This knowledge empowers healthcare systems to adapt, innovate and deliver high-quality care for a higher impact on patient outcomes.